1. Diabetic Ketoacidosis
Ramin Nazari, MD
Pediatric Critical Care Fellow
St. Christopher Hospital for Children
August 2012

2. Goals & Objectives
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Understand the pathophysiology of DKA
Understand the management approach to
the patient with DKA
Appreciate the complications that can occur
during treatment of DKA

3. Introduction
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▶
▶
▶
DKA is a serious acute complications of Diabetes Mellitus.
▶ Significant risk of death and/or morbidity especially with
delayed treatment.
The prognosis of DKA is worse in the extremes of age, with a
mortality rates of 5-10%.
With the new advances of therapy, DKA mortality decreased
to < 2%.
Before discovery and use of Insulin (1922) the mortality was
100%.

4. Epidemiology


DKA is characteristically associated with type 1 DM
It also occurs in type 2 diabetes
 Extreme stress
 Serious infection
 Trauma
 Cardiovascular
 Other emergencies

5. Pathophysiology
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Secondary to insulin deficiency, and the action of counterregulatory hormones, blood glucose increases leading to
hyperglycemia and glucosuria
Glucosuria
osmotic diuresis
water & Na loss
In the absence of insulin activity the body fails to utilize
glucose as fuel and uses fats instead
ketosis

6. Pathophysiology
‣ The excess of ketone bodies will cause metabolic acidosis,
the later is also aggravated by Lactic acidosis caused by
dehydration & poor tissue perfusion.
‣ Vomiting due to an ileus, plus increased insensible water
losses due to tachypnea will worsen the state of
dehydration.
‣ Electrolyte abnormalities are secondary to their loss in urine
& trans-membrane alterations following acidosis & osmotic
diuresis.

7. Pathophysiology
‣
‣
‣
‣
Because of acidosis, K ions enter the circulation leading to
hyperkalemia, this is aggravated by dehydration and renal
failure.
So, depending on the duration of DKA, serum K at diagnosis
may be high, normal or low, but the intracellular K stores are
always depleted.
Phosphate depletion will also take place due to metabolic
acidosis.
Na loss occurs secondary to the hyperosmotic state & the
osmotic diuresis

8. Pathophysiology

The dehydration can lead to decreased kidney perfusion and
acute renal failure.

Accumulation of ketone bodies contributes to the abdominal
pain and vomiting.

The increasing acidosis leads to acidotic breathing and
acetone smell in the breath and eventually causes impaired
consciousness and coma.

9. Signs and Symptoms
Polyuria, polydipsia
Enuresis
 Deahydrtion
Tachycardia
Orthostasis
 Abdominal pain
Nausea
Vomiting

Fruity breath
Acetone
 Kussmaul breathing
 Mental status changes
Combative
Drunk
Coma


10. Risk factors

Age <12 yrs

No first degree diabetic relative

Lower socioeconomic status

High dose glucocorticoids, atypical antipsychotics, diazoxide
and some immunosuppresive drugs

Poor access to medical care

Uninsured

11. Diagnosis
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Hyperglycemia (> 200 mg/dL)
ketones in the blood
Blood pH below 7.3
Serum bicarbonate level below 15 mEq/L
Venous pH <7.3 and/or bicarbonate <15 mmol/L
 mild DKA pH <7.3 bicarbonate <15
 moderate pH <7.2 bicarbonate <10
 severe
pH <7.1 bicarbonate < 5

12. Diagnostic Studies in DKA

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
Chemistry
 ↑ Glucose > 200
 ↓ Bicarbonate <15
 Anion gap = (Na+) – (Cl- + HCO3-)
 Frequently seen:

↑ BUN/creatinine
(dehydration)

↑ potassium

↓ sodium
Blood pH below 7.3
Serum acetones
 Positive in DKA
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Urinalysis
 Ketones (for DKA);
leukocyte esterase, WBC
(for UTI)
CBC
 Leukocytosis (possible
infection)
Amylase/Lipase
 To evaluate for pancreatitis
 BUT, DKA by itself can also
increase them!
EKG
 Evaluate for possible MI

13. Laboratory Evaluation
 Blood glucose
 Electrolytes and osmolality
 Bicarbonate, lactate
 Calcium and ionized Ca, Mg, P
BUN, creatinine
 Blood Gas
 CBC and hemoglobin A1c
 Blood beta hydroxybutyrate
 Urinalysis and urine for ketones
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If there is evidence of infection, culture:
 blood, urine, throat, wound
EKG for baseline evaluation of intracellular potassium status.

14. Treatment
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Monitoring
Consider ICU admission for closer monitoring if:
 Severe DKA (pH < 7.1 or < 7.2 in young child)
 Altered level of consciousness
 Under age of 5 years
 Increased risk for cerebral edema
Neurological status
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consider neuro checks q 1 hr
How does the patient look TO YOU?

15. Treatment
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Goals of treatment of DKA
 intravascular volume expansion
 correction of deficits in fluids, electrolytes, and acid-base
status
 initiation of insulin therapy to correct catabolism,
acidosis
Treatment is divided into 3 phases
 treatment of ketoacidosis
 transition period
 continuing phase and guidance

16. Fluid Therapy
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Assume 10-15% dehydration
Begin with a 10-20 ml/kg bolus of NS
Replace calculated deficit evenly over 36 hours generally 1.5 x maintenance for the next several hours
is appropriate
Do not exceed 40ml’s/kg in the initial 4 hours, or 4 L/m²
in 24 hours
Double bag system
 NS at 1.5 x M until glucose below 300 mg/dl
 D10 NS to be mixed with NS to achieve desired
glucose concentration

17. Insulin Therapy

IV infusion with basal rate 0.1 U/kg/hr

No initial insulin bolus – it will decrease time to correction of
the glucose, but does not alter the time to correction of
acidosis

It may decrease the serum osmolality more rapidly than
desirable

Ideal glucose decline is about 50-100 mg/hr

Continue insulin until urinary (blood) ketones are cleared

18. Potassium & Sodium
 Add
potassium when K< 5 and with urination
 K >5.5 – no potassium in IVF
 K 4.5 – 5.5 – 20 meq/L K+
 K <4.5 – 40 meq/L K+
 K supplementation
 20mEq/L K Acetate + 20mEq/L K Phosphate
 early replacement and frequent monitoring
 Pseudohyponatremia, add 1.6 mEq of Na to every 100mg/dL
of glucose above normal
 Expect that the Na+ level will rise during treatment
 If Na+ does not rise, true hyponatremia may be present (risk
of cerebral edema) and should be treated

19. Phosphate

Prevent depletion of RBC 2,3 DPG which will improve tissue
oxygenation as acidosis is resolving

May be useful in patients with anemia, CHF, pneumonia,
hypoxia

Ionized calcium is low, phosphorous should not be given

20. Bicarbonate
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Bicarbonate should be used only when there is severe
depression of the circulatory system or cellular metabolism
Not recommended unless pH <7.0, not even then, unless above
true
Bicarbonate administration leads to increased cerebral acidosis
HCO3- + H+ = CO2 + H2O.

Bicarbonate passes the BBB slowly
CO2 diffuses freely

exacerbating cerebral acidosis and cerebral depression


21. Complications
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Infection
 Precipitates DKA
 Fever
 Leukocytosis can be secondary to acidosis
Shock
 If not improving with fluids r/o MI
Vascular thrombosis
 Severe dehydration
 Cerebral vessels
 Occurs hours to days after DKA
Pulmonary Edema
 Result of aggressive fluid resuscitation
Cerebral Edema
 First 24 hours

22. Cerebral Edema
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Major cause of death in childhood DKA
 20% with cerebral edema die
 20% with mild to severe neurologic outcomes
At risk:
 Younger age
 Initial pH < 7.1
 Lower pCO2
 New onset
 Longer duration of symptom
 Rapid rehydration (> 50cc/ kg in first 4 hrs)
 Hypernatremia/ persistent hyponatremia
 Increased BUN
 Use of bicarbonate
 Lack of an increase in the serum Na during Therapy

23. Cerebral Edema-Pathophysiology
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The cause is not fully understood
May be present before treatment has begun, but more
commonly occurs 4 to 12 hours after the initiation of therapy
Numerous factors have been implicated in the
pathophysiology of DKA-related cerebral edema, but none
has been proven
 Ischemic
 Vasogenic
 Osmotic
 Cytotoxic processes

24. Cerebral Edema-Pathophysiology
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
Ischemia/cytotoxic edema
 Decrease of N-acetylaspartate (NAA), a marker of
neuronal function or viability in several areas of the brain
 Increased lactate production in the basal ganglia
Vasogenic edema
 Primary damage to the cerebral vascular endothelium
results in increased BBB permeability or a disturbance in
autoregulation, which permits abnormal diffusion of
intravascular fluids into the cerebral tissues

25. Cerebral Edema-Pathophysiology

Osmotic edema as a consequence of fluid therapy
 During the hyperosmolar state of DKA, the brain
produces Idiogenic Osmoles as a compensatory measure
to increase intracellular osmotic pressure and prevent
cerebral dehydration
 If the extracellular compartment is at a lower osmolarity
than the intracellular compartment, osmotic pressure
promotes water movement into the intracellular
compartment.
 During DKA, the combination of insulin and fluid
repletion lowers the serum glucose and plasma
osmolality, promoting osmotic water movement into the
brain

26. Cerebral Edema
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Usually develops several hours after the initiation of therapy
Manifestations:
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Headache
Change of mental status
Bradycardia and Hypertension
Sudden onset/return of vomiting
Unequal or fixed, dilated pupils
Treatment:
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Mannitol: 1 gram/ kg IV over 30 minutes
Elevate the head of the bed
Decrease IVF rate and insulin infusion rate
ICU management
Do not delay treatment until radiographic evidence

27. Case Scenario #1
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A 10 y/o male (~30 kg) presents to the ED with a one-day
history of emesis and lethargy.
Vitals show T 37C, HR 110, RR 25, BP 99/65. Patient is
lethargic, but oriented x 3. Exam reveals the odor of acetone
on the breath, dry lips, but otherwise unremarkable
Labs: pH 7.05, PaCO2 20, PaO2 100, BE -20, Na+ 133, K + 5.2, Cl
96, CO2 8, BS 600. Urine shows 4+ glucose and large ketones

28. Case Scenario #1
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How much fluid would you administer as a bolus?
Would you administer bicarbonate?
What is the “true” serum sodium?
How much insulin would you administer?
What IVF would you start? At what rate?

29. Case Scenario #2
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A 4 y/o female in the PICU is undergoing treatment for new
onset IDDM and DKA. She is on an insulin infusion at 0.1
u/kg/hr, and fluids are running at 2400 cc/m2/day.
Over the last hour, she has been complaining about
increasing headache. She is now found to be unresponsive
with bilateral fixed and dilated pupils, HR is 50 with BP
150/100.
What is your next step in management?

30. Case Scenario #3
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12 year old admitted with:
 pH = 7.0
 Na= 136, K=3.8, glucose 583mg/ dl
 She is oriented and conversant on admission, you follow
the DKA protocol,
2 hours later she becomes difficult to arouse and is
responsive only to deep pain.
What do you do?
Presume cerebral edema
 Decrease fluid infusion
 Give mannitol: 1 gm/kg